Particulated Juvenile Articular Cartilage Allograft for Treatment of Chondral Defects of the Knee: Short-Term Survivorship with Functional Outcomes.

While basic science research confirms the robust biological profile of juvenile chondrocytes, the clinical outcomes after particulated juvenile cartilage allograft transplantation are not well established. A retrospective analysis of active duty servicemembers undergoing surgical treatment with particulated juvenile articular cartilage allograft transplantation for chondral defects of the knee from two military treatment facilities was completed. Demographic variables, operative details, activity limitations, and medical discharges were obtained. A total of 29 patients with 36 treated chondral defects were isolated at an average follow-up of 16.2 months. The cohort was comprised of male service members in the Army with mean age of 33.1 years. Location of chondral lesion included the patellofemoral articulation (patella 39%, trochlea 31%, bipolar lesions 8%) and condyles (31%). Offloading or realignment osteotomy procedures were performed in 7 patients (23%). Of all patients, 14 servicemembers (48%) underwent knee-related medical discharge, and one patient underwent conversion to total knee arthroplasty. In this small patient cohort, particulated juvenile cartilage allograft transplantation for chondral defects of the knee did not reliably restore military servicemembers to full military function. At least one in two patients had persisting knee pain after chondral restoration procedure. (Journal of Surgical Orthopaedic Advances 30(1):010-013, 2021).

Protective effects of bestatin in the retina of streptozotocin-induced diabetic mice.

CD13/APN (aminopeptidase N) was first identified as a selective angiogenic marker expressed in tumor vasculature and is considered a target for anti-cancer therapy. CD13 was also reported to express in non-diabetic, hypoxia-induced retinal neovascularization. Whether diabetes induces upregulation of CD13 expression in the retina is unknown. We hypothesize that at an early stage of non-proliferative diabetic retinopathy (NPDR) characterized by disruption of blood-retinal barrier (BRB) permeability is related to upregulated expression of CD13 because of its known role in extracellular matrix (ECM) degradation. The purpose of this study is to evaluate the role of CD13/APN and the therapeutic efficacy of a CD13/APN inhibitor in a mouse model of streptozotocin-induced NPDR. Hyperglycemic C57Bl/6 mice 26 weeks after streptozotocin (STZ) injection were intravitreally injected with a sustained release formulation of CD13/APN inhibitor bestatin. At 15th day of post-bestatin treatment, mouse retinas were evaluated for vascular permeability by Evans blue dye extravasation assay, fluorescent angiography of retinal vascular permeability and leukostasis. Retinal protein extracts were analyzed by Western blot to determine the effects of bestatin treatment on the expression of CD13/APN related inflammatory mediators of ECM degradation and angiogenesis. Intravitreal bestatin treatment significantly inhibited retinal vascular permeability and leukostasis. This treatment also significantly inhibited retinal expression of CD13, ECM degrading proteases (heparanase and MMP9 and angiogenic molecules (HIF-1α and VEGF). Intravitreal CD13 inhibition may relate to furthering our knowledge on the protective effect of bestatin against diabetic retinal vasculature abnormalities through inhibition of retinal permeability, leukostasis, inflammatory molecules of ECM degradation and angiogenesis.

Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection.

The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography-mass spectroscopy (UPLC-MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at -20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation.

Potent Functional Immunogenicity of Plasmodium falciparum Transmission-Blocking Antigen (Pfs25) Delivered with Nanoemulsion and Porous Polymeric Nanoparticles.

PURPOSE: To evaluate functional immunogenicity of CHrPfs25. a malaria transmission blocking vaccine antigen, using nanoemulsion and porous polymeric PLGA nanoparticles. METHODS: CHrPfs25 was formulated with nanoemulsions (NE) and poly(D,L-lactide-co-glycolide) nanoparticles (PLGA-NP) and evaluated via IM route in mice. Transmission blocking efficacy of antibodies was evaluated by standard mosquito membrane feeding assay using purified IgG from immune sera. Physicochemical properties and stability of various formulations were evaluated by measuring poly-dispersity index, particle size and zeta potential. RESULTS: Mice immunized with CHrPfs25 using alum via IP and IM routes induced comparable immune responses. The highest antibody response was obtained with CHrPfs25 formulated in 4% NE as compared to 8% NE and PLGA-NP. No further increases were observed by combining NE with MPL-A and chitosan. One hundred percent transmission blocking activity was demonstrated at 400 µg/ml of IgG for alum groups (both routes IP and IM), 4% NE and NE-MPL-A. Purified IgG from various adjuvant groups at lower doses (100 µg/mL) still exhibited >90% transmission blocking activity, while 52-81% blocking was seen at 50 µg/mL. CONCLUSION: Results suggest that CHrPfs25 delivered in various adjuvants/nanoparticles elicited strong functional immunogenicity in pre-clinical studies in mice. We are now continuing these studies to develop effective vaccine formulations for further evaluation of immune correlates of relative immunogenicity of CHrPfs25 in various adjuvants and clinical trials.

An ultra-high performance chromatographic method for the determination of artemisinin.

OBJECTIVE: The goal of this study is to develop an ultra-high performance liquid chromatographic method for the quantitative determination of artemisinin at very low concentrations using selective ion mass spectroscopic detection. MATERIALS AND METHODS: Separation was conducted using a C4 100 mm× 2.1 mm column, and the mobile phase consisted of an isocratic two-component system consisting of 60% of a 0.1% aqueous solution of formic acid and 40% acetonitrile at a flow rate of 0.4 ml/min. The drug was detected by means of an electrospray mass spectrometer with selective ion monitoring of the [M-H2O+H](+) with m/z of 265.3 in positive ion mode. RESULTS: The calibration curves of artemisinin obtained from the UPLC/MS system were linear in the three ranges analyzed, with a correlation coefficient of no less than 0.9996 for all sets of standards. The peak tailing factor for all measurements were ≤1.7. The method proved to have good repeatability and linearity. DISCUSSION: The described analytical method reached a LOQ of 0.010 µg/ml with an isocratic system and enables an analysis rate of 20 samples per hour. The linearity of the standards was excellent for all sets of standards analyzed. CONCLUSION: The method presented in this study provides a rapid and suitable means for the determination of artemisinin at very low concentrations. This is especially significant when performing dissolution studies where, due to the low solubility of artemisinin, a method that can measure the drug at nanogram levels is necessary.

Development and in vitro evaluation of a nanoemulsion for transcutaneous delivery.

OBJECTIVE: The purpose of this study is to develop a nanoemulsion formulation for its use as a transcutaneous vaccine delivery system. MATERIALS AND METHODS: With bovine albumin-fluorescein isothiocyanate conjugate (FITC-BSA) as a vaccine model, formulations were selected with the construction of pseudo-ternary phase diagrams and a short-term stability study. The size of the emulsion droplets was furthered optimized with high-pressure homogenization. The optimized formulation was evaluated for its skin permeation efficiency. In vitro skin permeation studies were conducted with shaved BALB/c mice skin samples with a Franz diffusion cell system. Different drug concentrations were compared, and the effect of the nanoemulsion excipients on the permeation of the FITC-BSA was also studied. RESULTS: The optimum homogenization regime was determined to be five passes at 20 000 psi, with no evidence of protein degradation during processing. With these conditions, the particle diameter was 85.2 nm ± 15.5 nm with a polydispersity index of 0.186 ± 0.026 and viscosity of 14.6 cP ± 1.2 cP. The optimized formulation proved stable for 1 year at 4 °C. In vitro skin diffusion studies show that the optimized formulation improves the permeation of FITC-BSA through skin with an enhancement ratio of 4.2 compared to a neat control solution. Finally, a comparison of the skin permeation of the nanoemulsion versus only the surfactant excipients resulted in a steady state flux of 23.44 µg/cm(2)/h for the nanoemulsion as opposed to 6.10 µg/cm(2)/h for the emulsifiers. CONCLUSION: A novel nanoemulsion with optimized physical characteristics and superior skin permeation compared to control solution was manufactured. The formulation proposed in this study has the flexibility for the incorporation of a variety of active ingredients and warrants further development as a transcutaneous vaccine delivery vehicle.

Physiochemical and Microbiological Stability of Azathioprine Suspensions in PCCA Base, SuspendIt.

Azathioprine is used to treat the symptoms of rheumatoid arthritis and for the prevention of transplant rejection. A review of the therapeutic uses of Azathioprine reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of Azathioprine currently exists. Azathioprine is commercially available only as a 50-mg tablet. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded Azathioprine suspensions in the PCCA Base, SuspendIt. This base is a sugar-free, paraben free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two Azathioprine concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of Azathioprine in PCCA SuspendIt was developed and validated. Suspensions of Azathioprine were prepared in PCCA SuspendIt at 10-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 49, 63, 90, 119, and 182. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that Azathioprine concentrations did not go below 96.8% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. The pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that Azathioprine is physically, chemically, and microbiologically stable in PCCA SuspendIt for 182 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for Azathioprine in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Physicochemical and Microbiological Stability of Pyrimethamine in Paraben-free PCCA Base, SuspendIt.

Pyrimethamine is an antiparasitic compound available only in tablet form for oral administration. A review of the therapeutic uses of pyrimethamine reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of pyrimethamine currently exists. Pyrimethamine is available commercially only as 25-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded pyrimethamine suspension in PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of pyrimethamine in PCCA SuspendIt was developed and validated. Suspensions of pyrimethamine were prepared in PCCA SuspendIt at a 2-mg/mL concentration, selected to provide flexibility in customizing individual doses. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, and 42. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that pyrimethamine concentrations did not go below 96% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that pyrimethamine is physically, chemically, and microbiologically stable in PCCA SuspendIt for 42 days stored in the refrigerator and at room temperature, thus providing a viable, compounded alternative for pyrimethamine in a liquid dosage form.

Physicochemical and Microbiological Stability of Amitriptyline Hydrochloride Oral Liquid Dosage Forms in PCCA Base, SuspendIt.

Amitriptyline hydrochloride is indicated for the relief of symptoms of depression. A review of the therapeutic uses of amitriptyline hydrochloride reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of amitriptyline currently exists. Amitriptyline hydrochloride is commercially available only as 10-mg, 25-mg, 50-mg, 75-mg, 100-mg, and 150-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded amitriptyline hydrochloride suspensions in PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two amitriptyline hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability- indicating high-performance liquid chromatographic assay for the determination of the chemical stability of amitriptyline hydrochloride in PCCA SuspendIt was developed and validated. Suspensions of amitriptyline hydro- chloride were prepared in PCCA SuspendIt at 1-mg/mL and 5-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 49, 63, 91, 119, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that amitriptyline hydrochloride concentrations did not go below 99.8% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. The pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that amitriptyline hydrochloride is physically, chemically, and microbiologically stable in PCCA SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for amitriptyline hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Physicochemical and Microbiological Stability of Compounded Metronidazole Suspensions in PCCA SuspendIt.

Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be individualized in the treatment of trichomoniasis, in patients with hepatic impairment, and in pediatric as well as geriatric patients. A review of the therapeutic uses of metronidazole reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of metronidazole currently exists. Metronidazole is commercially available only as 250-mg and 500-mg film-coated tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded metronidazole suspensions in PCCA SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two metronidazole concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatographic assay for the determination of the chemical stability of metronidazole in PCCA SuspendIt was developed and validated. Suspensions of metronidazole were prepared in PCCA SuspendIt at 25-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5ÆC and 25ÆC). Samples were assayed initially and on the following time points (days): 7, 14, 28, 42, 59, 90, 122, and 180. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was also tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that metronidazole concentrations did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values also did not change significantly. This study demonstrates that metronidazole is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for metronidazole in a liquid dosage form, with an extended beyond-use-date to meet patient needs.

Physicochemical and Microbiological Stability of Extemporaneously Compounded Hydrocortisone Oral Suspensions in PCCA Base, SuspendIt.

Hydrocortisone is indicated in the treatment of primary or secondary adrenal insufficiency. The oral dosage regimen of hydrocortisone needs to be individualized in the treatment of congenital adrenal hyperplasia, especially in pediatric patients. A review of the therapeutic uses of hydrocortisone reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of hydrocortisone currently exists. Hydrocortisone is commercially available as 5-mg, 10-mg, and 20-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded hydrocortisone suspensions in PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two hydrocortisone concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of hydrocortisone in SuspendIt was developed and validated. Suspensions of hydrocortisone were prepared in SuspendIt at 1-mg/mL and 20-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially and on the following days: 7, 15, 28, 45, 60, 91, 120, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that hydrocortisone concentrations did not go below 94% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values did not change significantly. This study demonstrates that hydrocortisone is physically, chemically, and microbiologically stable in SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for hydrocortisone in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Controlled release multiple layer coatings.

PURPOSE: In a fluid-bed coating machine, the coating solutions are normally sprayed using a manually controlled peristaltic pump. This study provides a process where two or more coating solutions can be sprayed consecutively using two or more syringe pumps controlled by a computer, to form multiple layers. In this process, the spraying parameters can be controlled easily from a computer. METHODS: Propranolol HCl was used as a model drug. Nine different drug-loaded controlled release coated beads were prepared by using a combination of ethylcellulose and/or chitosan solutions. The pulse-coated beads were prepared by changing the spray rate and/or volume of the polymer solutions. RESULTS: There was a fourfold increase (18 versus 75 minutes) in lag time when the same amount of ethylcellulose (4 g) was dissolved in 100 mL of ethanol instead of 160 mL. When the same amount of drug and ethylcellulose solution was applied on the acrylic coated beads as multiple layers coating, the lag time decreased to only 6 minutes. Similarly, the 50% drug release time also decreased significantly. CONCLUSION: An overall comparison of the dissolution profiles showed that drug release from these coated beads was changed significantly when the sequence of the drug and polymer layers was changed.

Composite bone and soft tissue loss treated with distraction histiogenesis.

The purpose of this article is to describe the use of shortening and angulation to manage composite bone and soft tissue loss associated with combat-related type IIIB open tibia fractures. Four patients underwent placement of a software-driven circular fixator with acute shortening and angulation to manage composite bone and soft tissue loss. Frames were applied using the Rings First Method, and an induced deformity was created with the soft tissue defect within the concavity. Distraction histiogenesis was utilized to restore limb length and regenerate soft tissues. Three patients had healed fractures and mature regenerate allowing frame removal, while one remained in his frame for further consolidation. Mechanical alignment and limb length were restored in all patients. No major frame adjustments were required and all distracted soft tissues healed without complication. The article concludes that composite bone and soft tissue loss is effectively managed with distraction histiogenesis and the use of a software-driven circular fixator.

Physicochemical Stability of Compounded Allopurinol Suspensions in PCCA Base, SuspendIt.

Allopurinol is an orally administered inhibitor of xanthine oxidase used primarily in the treatment of hyperuricemia associated with gout. Allopurinol reduces serum and urinary uric acid concentrations. Its use should be individualized for each patient. The dosage of allopurinol to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease, and needs to be flexible to permit precise, customized dose titration for individual patients. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of allopurinol currently exists. Allopurinol is commercially available as 100-mg and 300-mg scored tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded allopurinol suspensions in the PCCA Base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two allopurinol concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatography assay for the determination of the chemical stability of allopurinol in SuspendIt was developed and validated. Suspensions of allopurinol were prepared in SuspendIt at 10.0-mg/mL and 20.0-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially and at the following time points: 7 days, 14 days, 30 days, 45 days, 60 days, 88 days, 120 days, and 182 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. The study showed that allopurinol concentrations did not go below 93% of the label claim (initial drug concentration) at both temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that allopurinol is physically and chemically stable in SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for allopurinol in a liquid dosage form, with an extended beyond-use-date to meet patient needs.

Spray-dried chitosan as a direct compression tableting excipient.

The objective of this study was to prepare and evaluate a novel spray-dried tableting excipient using a mixture of chitosan and lactose. Three different grades of chitosan (low-, medium-, and high-molecular-weight) were used for this study. Propranolol hydrochloride was used as a model drug. A specific amount of chitosan (1, 1.9, and 2.5 g, respectively) was dissolved in 50 mL of an aqueous solution of citric acid (1%) and later mixed with 50 mL of an aqueous solution containing lactose (20, 19.1, and 18.5 g, respectively) and propanolol (2.2 g). The resultant solution was sprayed through a laboratory spray drier at 1.4 mL/min. The granules were evaluated for bulk density, tap density, Carr index, particle size distribution, surface morphology, thermal properties, and tableting properties. Bulk density of the granules decreased from 0.16 to 0.13 g/mL when the granules were prepared using medium- or high-molecular-weight chitosan compared with the low-molecular-weight chitosan. The relative proportion of chitosan also showed a significant effect on the bulk density. The granules prepared with 1 g of low-molecular-weight chitosan showed the minimum Carr index (11.1%) indicating the best flow properties among all five formulations. All three granules prepared with 1 g chitosan, irrespective of their molecular weight, showed excellent flow properties. Floating tablets prepared by direct compression of these granules with sodium bicarbonate showed 50% drug release between 30 and 35 min. In conclusion, the spray-dried granules prepared with chitosan and lactose showed excellent flow properties and were suitable for tableting.

Physicochemical Stability of Compounded Amlodipine Besylate Suspensions in PCCA Base, SuspendIt.

Amlodipine besylate is an antihypertensive agent recommended for the management of hypertension in children and adolescents. The commercially available 2.5-mg, 5-mg, and 10-mg amlodipine besylate tablets do not provide the necessary flexibility in dosing needed for treating children. This flexibility is readily achieved using an oral, liquid dosage form. However, no commercial liquid dosage form of amlodipine currently exists. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded amlodipine besylate suspensions in the PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two amlodipine besylate concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stabilityindicating high-performance liquid chromatographic assay for the determination of the chemical stability of amlodipine besylate in SuspendIt was developed and validated. Suspensions of amlodipine were prepared in SuspendIt at 0.5-mg/mL and 10.0-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and at the following time points: 7 days, 14 days, 29 days, 46 days, 60 days, 90 days, 120 days, and 180 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. This study demonstrates that amlodipine besylate is physically and chemically stable in SuspendIt for 90 days in the refrigerator and 7 days at room temperature, retaining 90% of the label claim (initial drug concentration) at both concentrations. The pH values did not change significantly. The viscosity of the refrigerated samples at both concentrations decreased slightly, while that of the room temperature samples showed a marked increase in viscosity. This study provides a viable, compounded alternative for amlodipine in a liquid dosage form, with an adequate beyond-use-date to meet patient needs. The study further provides stability documentation over a bracketed amlodipine concentration range of 0.5 mg/mL to 10.0 mg/mL, allowing compounding pharmacists more flexibility in customizing their formulations.

Stability of Compounded Ursodiol Suspensions in PCCA Base, SuspendIt.

Ursodiol (ursodeoxycholic acid) is a nontoxic, naturally occurring bile acid that constitutes 1% to 2% of human bile. It suppresses hepatic synthesis of cholesterol, aids in the desaturation of biliary cholesterol, and aids in the dissolution of cholesterol gallstones. Ursodiol is commercially available as a 300-mg capsule and a 250-mg tablet. However, no commercial liquid dosage form of ursodiol exists. An extemporaneously compounded suspension from pure drug powder or commercial tablets/capsules would provide an alternative option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded ursodiol suspensions in PCCA base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. It thickens upon standing to minimize settling of any insoluble drug particles and becomes fluid upon shaking to allow convenient pouring during administration to the patient. The study design included two ursodiol concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust, stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of ursodiol in SuspendIt was developed and validated. Suspensions of ursodiol were prepared in SuspendIt at 50-mg/mL and 100-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially and at the following time points: 7 days, 14 days, 30 days, 42 days, 59 days, 91 days, 120 days, and 181 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. The study showed that ursodiol concentration did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that ursodiol is physically and chemically stable in SuspendIt for 181 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for ursodiol in a liquid-dosage form, with an extended beyond-use-date to meet patient needs.

Physicochemical Stability of Compounded Naltrexone Hydrochloride Solutions in PCCA Base SuspendIt.

Naltrexone hydrochloride is an orally active narcotic antagonist used to facilitate rapid transition from methadone maintenance. The dosing schedule of naltrexone hydrochloride in detoxification protocols needs to be flexible to permit precise, customized dose titration for individual patients. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of naltrexone hydrochloride currently exists. Naltrexone hydrochloride is commercially available as a scored, filmcoated, 50-mg tablet. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded naltrexone hydrochloride solutions in PCCA base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two naltrexone hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating HPLC assay for the determination of the chemical stability of naltrexone hydrochloride in SuspendIt was developed and validated. Solutions of naltrexone hydrochloride were prepared in SuspendIt at 0.5-mg/mL and 5.0-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic, amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and at the following time points: 7 days, 14 days, 29 days, 44 days, 61 days, 90 days, 120 days, and 180 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous preparation is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. The study showed that naltrexone hydrochloride concentrations did not go below 94% of the label claim (initial drug concentration) at both temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that naltrexone hydrochloride is physically and chemically stable in SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for naltrexone hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Preparation of polylactide-co-glycolide and chitosan hybrid microcapsules of amifostine using coaxial ultrasonic atomizer with solvent evaporation.

The objective of this study was to evaluate the effect of various processing and formulation factors on the characteristics of amifostine hybrid microcapsules. Amifostine-loaded hybrid microcapsules were prepared using PLGA and chitosan. In short, amifostine powder was dissolved in de-aerated water with or without chitosan. The amifostine solution was later emulsified into PLGA solution in dichloromethane containing phosphatidylcholine. The resultant emulsion was fed through the inner capillary of a coaxial ultrasonic atomizer. The liquid fed through the coaxial outer capillary was either water or chitosan solution. The atomized droplets were collected into PVA solution and the droplets formed microcapsules immediately. The hybrid microcapsules prepared with chitosan solution only as an outer layer liquid showed the maximum efficiency of encapsulation (30%). The median sizes of all three formulations were 33-44 microm. These formulations with chitosan showed positive zeta-potential and sustained drug release with 13-45% amifostine released in 24 h. When chitosan was incorporated into inner as well as outer liquid layers, the drug release increased significantly, 45% (compared with other formulations) released in 24 h and almost 100% released in 11 days. Hybrid microcapsules of amifostine showed moderately high efficiency of encapsulation. The cationic charge (due to the presence of chitosan) of these particles is expected to favour oral absorption and thus overall bioavailability of orally administered amifostine.

Polymicrobial skull osteomyelitis: a rare complication of subdural hematoma evacuation.

BACKGROUND: Osteomyelitis of the skull (SO) is a rare condition. The infection may complicate community-acquired sinusitis, otitis, or mastoiditis, in which case, the skull base is affected most commonly. The flora typically seen in these conditions, such as Streptococcus pneumoniae and Haemophilus influenzae, tends also to be responsible for the SO. Osteomyelitis also may follow neurosurgical procedures that breach the skull, in which case, the pathogens frequently are typical cutaneous flora such as Staphylococcus aureus or coagulase-negative staphylococci. METHODS: A case report of post-neurosurgical SO and a review of the relevant English-language literature. RESULTS: We report a delayed presentation of SO after craniotomy for the evacuation of a chronic subdural hematoma. Cranial tissue cultures grew Staphylococcus aureus, Corynebacterium spp., and Escherichia coli. CONCLUSIONS: The isolation of Escherichia coli as an infecting organism in SO has been reported rarely and may reflect a unique pathogenesis.